Our research has focused on the somatic cell genetics and molecular biology of cell surface proteins. The basic approach is to isolate, from mouse cells in culture, mutants that have undergone changes in the expression or structure of cell surface proteins coded for by genes in the major histocompatibility complex (MHC). Two general areas of interest are pursued. One major area of investigation is to study the control of gene expression. Several mutants have been isolated that no longer express some or all of the genes of the MHC. When these mutants are analyzed by Southern blotting technique, the fragments of DNA that are known to contain the nonexpressed genes are missing. Evidence accumulated in the lab strongly suggest that the mechanism for this phenomenon is not simple chromosome loss, but somatic crossing over. Since mitotic recombination has never before been described in a mammalian cell and since this process offers a rapid and reliable way for genetic mapping, this area is being pursued actively. The other major area of interest is the study of structure-function relationships in the products of genes of the MHC. It is now becoming clear that proteins coded for by the MHC play a crucial role in the recognition, by the body's immune system, of cells that are infected by viruses. The exact role played by the MHC proteins is not clear. This area is being approached by isolating mutant cell lines which express altered forms of MHC proteins. Thus, using hybridoma antibodies, mutants have been isolated that express point mutations in several of the MHC proteins. The effect of such mutations on the recognition by the immune system of virus infection is being analyzed.